Letter abstract
Nature Biotechnology 25, 132 - 138 (2006)
Published online: 31 December 2006 | doi:10.1038/nbt1271
Production of cattle lacking prion protein
Jürgen A Richt1,6, Poothappillai Kasinathan2, Amir N Hamir1, Joaquin Castilla3, Thillai Sathiyaseelan2, Francisco Vargas1, Janaki Sathiyaseelan2, Hua Wu2, Hiroaki Matsushita2, Julie Koster2, Shinichiro Kato4,5, Isao Ishida4, Claudio Soto3, James M Robl2 & Yoshimi Kuroiwa4,5,6
Abstract
Prion diseases are caused by propagation of misfolded forms of the normal cellular prion protein PrPC, such as PrPBSE in bovine spongiform encephalopathy (BSE) in cattle and PrPCJD in Creutzfeldt-Jakob disease (CJD) in humans1. Disruption of PrPC expression in mice, a species that does not naturally contract prion diseases, results in no apparent developmental abnormalities2, 3, 4, 5. However, the impact of ablating PrPC function in natural host species of prion diseases is unknown. Here we report the generation and characterization of PrPC-deficient cattle produced by a sequential gene-targeting system6. At over 20 months of age, the cattle are clinically, physiologically, histopathologically, immunologically and reproductively normal. Brain tissue homogenates are resistant to prion propagation in vitro as assessed by protein misfolding cyclic amplification7. PrPC-deficient cattle may be a useful model for prion research and could provide industrial bovine products free of prion proteins.
- National Animal Disease Center, Agriculture Research Services, United States Department of Agriculture, 2300 Dayton Avenue, Ames, Iowa 50010, USA.
- Hematech, Inc., 4401 S. Technology Drive, Sioux Falls, South Dakota 57106, USA.
- Department of Neurology, University of Texas Medical Branch, 301 University Boulevard, Galveston, Texas, 77555-0646, USA.
- Pharmaceutical Division, Kirin Brewery Co., Ltd., 26-1, Jingumae 6-chome, Shibuya-ku, Tokyo, Japan.
- Gemini Science Inc., 9420 Athena Circle, La Jolla, California 92109, USA.
- These authors contributed equally to this work.
Correspondence to: Yoshimi Kuroiwa4,5,6 e-mail: ykuroiwa@hematech.com
Correspondence to: James M Robl2 e-mail: jrobl@hematech.com
Correspondence to: Jürgen A Richt1,6 e-mail: jricht@nadc.ars.usda.gov
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